Chaperones

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Revision as of 11:37, 19 June 2014

spinqualitylabelsall models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Chaperones are proteins that are involved in the folding and unfolding of other macromolecules. The word chaperone means 'giving protection' which implies the idea of preventing new proteins from misfolding. They exists both in prokaryotes and eukaryotes. Some chaperones are constitutively expressed in the system where as other chaperones are expressed only in response to an external stimulus or stress such as heat and therefore they are referred to as heat shock proteins. They are classified based on their structure, size, molecular weight and function in to several classes such as Hsp40s, Hsp60s Chaperonin, Hsp70s, Hsp90s such as 1am1, Hsp100s and small heat shock proteins like (alpha)-crystallin proteins. Various classes of molecular chaperones cooperate for the folding of the nascent polypeptide chains in the cyotplasm [1]. Contents 1 Function 2 Disease 3 Relevance 4 Structural highlights Function Chaperones bind to the newly synthesized and unfolded proteins helping them acquire their properly folded 3D structure [2]. Besides, chaperones help in targeting the native proteins to their respective organelles [3][4]. The first identified chaperones were the histone chaperones that are continously involved in histone metabolism thus regulating genome function, stability and identity[5]. Many protozoan parasites such as Plasmodium falciparum requires these proteins for cytoprotection [6] [7]. Chaperones actively participate in the maintenance of proteome integrity and protein homeostasis (proteostasis) which requires a syncrhonization in various chaperone's tuning the process [8]. Disease Chaperones are instrumental in protein folding processes. Alteration in this process may lead to protein aggregation and formation of inclusion bodies. Protein misfolding may result in various diseases such as Alzheimer [9], Parkinson [10], Familial amyotrophic lateral sclerosis [11], Huntington[12], Spinobulbar muscular atrophy [13] and ageing [14]. Relevance Modulation of chaperone's expression is a new therapeutic approach for the neurodegenerative and other diseases arising from protein misfolding. There is a distinct network of chaperones and co chaperones that either directly influences the substrate proteins or in association with the protein degradation pathways such as the ubiquitin-proteasome-system or autophagy, results in the removal of completely misfolded and pathogenic proteins[15]. Structural highlights Structurally, have a N-terminal followed by a . These domains the hsp70 functioning. is a representative example of a chaperone system in complex with ADP. In the 2D figure given below, panel A indicates the various folded (green) and unfolded (red)regions in Hsp70. Panel B shows the structural organization of Hsp 70 indicating its various domains. ATP binding and hydrolysis regulates the affinity for substrate proteins which thereafter enhances ATP hydrolysis. Image:1-s2.0-S0301462209000520-gr1.jpg Structural organization of Hsp70

References

1. ↑ Kim YE, Hipp MS, Bracher A, Hayer-Hartl M, Hartl FU. Molecular chaperone functions in protein folding and proteostasis. Annu Rev Biochem. 2013;82:323-55. doi: 10.1146/annurev-biochem-060208-092442. PMID:23746257 doi:http://dx.doi.org/10.1146/annurev-biochem-060208-092442
2. ↑ Ellis J. Proteins as molecular chaperones. Nature. 1987 Jul 30-Aug 5;328(6129):378-9. PMID:3112578 doi:http://dx.doi.org/10.1038/328378a0
3. ↑ Deshaies RJ, Koch BD, Werner-Washburne M, Craig EA, Schekman R. A subfamily of stress proteins facilitates translocation of secretory and mitochondrial precursor polypeptides. Nature. 1988 Apr 28;332(6167):800-5. PMID:3282178 doi:http://dx.doi.org/10.1038/332800a0
4. ↑ Halperin L, Jung J, Michalak M. The many functions of the endoplasmic reticulum chaperones and folding enzymes. IUBMB Life. 2014 May 19. doi: 10.1002/iub.1272. PMID:24839203 doi:http://dx.doi.org/10.1002/iub.1272
5. ↑ Gurard-Levin ZA, Quivy JP, Almouzni G. Histone chaperones: assisting histone traffic and nucleosome dynamics. Annu Rev Biochem. 2014 Jun 2;83:487-517. doi:, 10.1146/annurev-biochem-060713-035536. PMID:24905786 doi:http://dx.doi.org/10.1146/annurev-biochem-060713-035536
6. ↑ Matambo TS, Odunuga OO, Boshoff A, Blatch GL. Overproduction, purification, and characterization of the Plasmodium falciparum heat shock protein 70. Protein Expr Purif. 2004 Feb;33(2):214-22. PMID:14711509
7. ↑ Misra G, Ramachandran R. Hsp70-1 from Plasmodium falciparum: protein stability, domain analysis and chaperone activity. Biophys Chem. 2009 Jun;142(1-3):55-64. doi: 10.1016/j.bpc.2009.03.006. Epub 2009 , Mar 16. PMID:19339102 doi:http://dx.doi.org/10.1016/j.bpc.2009.03.006
8. ↑ Kim YE, Hipp MS, Bracher A, Hayer-Hartl M, Hartl FU. Molecular chaperone functions in protein folding and proteostasis. Annu Rev Biochem. 2013;82:323-55. doi: 10.1146/annurev-biochem-060208-092442. PMID:23746257 doi:http://dx.doi.org/10.1146/annurev-biochem-060208-092442
9. ↑ Meriin AB, Sherman MY. Role of molecular chaperones in neurodegenerative disorders. Int J Hyperthermia. 2005 Aug;21(5):403-19. PMID:16048838 doi:http://dx.doi.org/10.1080/02656730500041871
10. ↑ Winklhofer KF, Tatzelt J. The role of chaperones in Parkinson's disease and prion diseases. Handb Exp Pharmacol. 2006;(172):221-58. PMID:16610362
11. ↑ Jain MR, Ge WW, Elkabes S, Li H. Amyotrophic lateral sclerosis: Protein chaperone dysfunction revealed by proteomic studies of animal models. Proteomics Clin Appl. 2008 May 1;2(5):670-684. PMID:19578526 doi:http://dx.doi.org/10.1002/prca.200780023
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